Radiomics Correlation to CD68+ Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME. METHODS: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering. RESULTS: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively. CONCLUSION: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies.

Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

Sarcopenia and body fat change as risk factors for radiologic incisional hernia following robotic nephrectomy.

OBJECTIVE: To assess the effect of body muscle and fat metrics on the development of radiologic incisional hernia (IH) following robotic nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent robotic nephrectomy for kidney tumors between 2011 and 2017. All pre- and postoperative CTs were re-reviewed by experienced radiologists for detection of radiologic IH and calculation of the following metrics using Synapse 3D software: cross-sectional psoas muscle mass at the level of L3 and L4 as well as subcutaneous and visceral fat areas. Sarcopenia was defined as psoas muscle index below the lowest quartile. Cox proportional hazard model was constructed to examine the association between muscle and fat metrics and the risk of developing radiologic IH. RESULTS: A total of 236 patients with a median (IQR) age of 64 (54-70) years were included in this study. In a median (IQR) follow-up of 23 (14-38) months, 62 (26%) patients developed radiologic IH. On Cox proportional hazard model, we were unable to detect an association between sarcopenia and risk of IH development. In terms of subcutaneous fat change from pre-op, both lower and higher values were associated with IH development (HR (95% CI) 2.1 (1.2-3.4), p = 0.01 and 2.4 (1.4-4.1), p < 0.01 for < Q1 and ≥ Q3, respectively). Similar trend was found for visceral fat area changes from pre-op with a HR of 2.8 for < Q1 and 1.8 for ≥ Q3. CONCLUSION: Both excessive body fat gain and loss are associated with development of radiologic IH in patients undergoing robotic nephrectomy.

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

CT-based radiomics stratification of tumor grade and TNM stage of clear cell renal cell carcinoma.

OBJECTIVES: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV). METHODS: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC). RESULTS: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification. CONCLUSION: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC. KEY POINTS: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively.

Whole-tumor 3D volumetric MRI-based radiomics approach for distinguishing between benign and malignant soft tissue tumors.

OBJECTIVES: Our purpose was to differentiate between malignant from benign soft tissue neoplasms using a combination of MRI-based radiomics metrics and machine learning. METHODS: Our retrospective study identified 128 histologically diagnosed benign (n = 36) and malignant (n = 92) soft tissue lesions. 3D ROIs were manually drawn on 1 sequence of interest and co-registered to other sequences obtained during the same study. One thousand seven hundred eight radiomics features were extracted from each ROI. Univariate analyses with supportive ROC analyses were conducted to evaluate the discriminative power of predictive models constructed using Real Adaptive Boosting (Adaboost) and Random Forest (RF) machine learning approaches. RESULTS: Univariate analyses demonstrated that 36.89% of individual radiomics varied significantly between benign and malignant lesions at the p ≤ 0.05 level. Adaboost and RF performed similarly well, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81), respectively, after 10-fold cross-validation. Restricting the machine learning models to only sequences extracted from T2FS and STIR sequences maintained comparable performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84), respectively. CONCLUSION: Machine learning decision classifiers constructed from MRI-based radiomics features show promising ability to preoperatively discriminate between benign and malignant soft tissue masses. Our approach maintains applicability even when the dataset is restricted to T2FS and STIR fluid-sensitive sequences, which may bolster practicality in clinical application scenarios by eliminating the need for complex co-registrations for multisequence analysis. KEY POINTS: • Predictive models constructed from MRI-based radiomics data and machine learning-augmented approaches yielded good discriminative power to correctly classify benign and malignant lesions on preoperative scans, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81) for Real Adaptive Boosting (Adaboost) and Random Forest (RF), respectively. • Restricting the models to only use metrics extracted from T2 fat-saturated (T2FS) and Short-Tau Inversion Recovery (STIR) sequences yielded similar performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84) for Adaboost and RF, respectively. • Radiomics-based machine learning decision classifiers constructed from multicentric data more closely mimic the real-world practice environment and warrant additional validation ahead of prospective implementation into clinical workflows.

Shape and texture-based radiomics signature on CT effectively discriminates benign from malignant renal masses.

OBJECTIVES: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model. MATERIALS AND METHODS: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC. RESULTS: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively. CONCLUSION: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics. KEY POINTS: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

Identification of robust and reproducible CT-texture metrics using a customized 3D-printed texture phantom.

OBJECTIVE: The objective of this study was to evaluate the robustness and reproducibility of computed tomography-based texture analysis (CTTA) metrics extracted from CT images of a customized texture phantom built for assessing the association of texture metrics to three-dimensional (3D) printed progressively increasing textural heterogeneity. MATERIALS AND METHODS: A custom-built 3D-printed texture phantom comprising of six texture patterns was used to evaluate the robustness and reproducibility of a radiomics panel under a variety of routine abdominal imaging protocols. The phantom was scanned on four CT scanners (Philips, Canon, GE, and Siemens) to assess reproducibility. The robustness assessment was conducted by imaging the texture phantom across different CT imaging parameters such as slice thickness, field of view (FOV), tube voltage, and tube current for each scanner. The texture panel comprised of 387 features belonging to 15 subgroups of texture extraction methods (e.g., Gray-level Co-occurrence Matrix: GLCM). Twelve unique image settings were tested on all the four scanners (e.g., FOV125). Interclass correlation two-way mixed with absolute agreement (ICC3) was used to assess the robustness and reproducibility of radiomic features. Linear regression was used to test the association between change in radiomic features and increased texture heterogeneity. Results were summarized in heat maps. RESULTS: A total of 5612 (23.2%) of 24 090 features showed excellent robustness and reproducibility (ICC ≥ 0.9). Intensity, GLCM 3D, and gray-level run length matrix (GLRLM) 3D features showed best performance. Among imaging variables, changes in slice thickness affected all metrics more intensely compared to other imaging variables in reducing the ICC3. From the analysis of linear trend effect of the CTTA metrics, the top three metrics with high linear correlations across all scanners and scanning settings were from the GLRLM 2D/3D and discrete cosine transform (DCT) texture family. CONCLUSION: The choice of scanner and imaging protocols affect texture metrics. Furthermore, not all CTTA metrics have a linear association with linearly varying texture patterns.

Benchmarking Various Radiomic Toolkit Features While Applying the Image Biomarker Standardization Initiative toward Clinical Translation of Radiomic Analysis.

The image biomarkers standardization initiative (IBSI) was formed to address the standardization of extraction of quantifiable imaging metrics. Despite its effort, there remains a lack of consensus or established guidelines regarding radiomic feature terminology, the underlying mathematics and their implementation across various software programs. This creates a scenario where features extracted using different toolboxes cannot be used to build or validate the same model leading to a non-generalization of radiomic results. In this study, IBSI-established phantom and benchmark values were used to compare the variation of the radiomic features while using 6 publicly available software programs and 1 in-house radiomics pipeline. All IBSI-standardized features (11 classes, 173 in total) were extracted. The relative differences between the extracted feature values from the different software programs and the IBSI benchmark values were calculated to measure the inter-software agreement. To better understand the variations, features are further grouped into 3 categories according to their properties: 1) morphology, 2) statistic/histogram and 3)texture features. While a good agreement was observed for a majority of radiomics features across the various tested programs, relatively poor agreement was observed for morphology features. Significant differences were also found in programs that use different gray-level discretization approaches. Since these software programs do not include all IBSI features, the level of quantitative assessment for each category was analyzed using Venn and UpSet diagrams and quantified using two ad hoc metrics. Morphology features earned lowest scores for both metrics, indicating that morphological features are not consistently evaluated among software programs. We conclude that radiomic features calculated using different software programs may not be interchangeable. Further studies are needed to standardize the workflow of radiomic feature extraction.

Texture Analysis of Imaging: What Radiologists Need to Know.

OBJECTIVE: Radiologic texture is the variation in image intensities within an image and is an important part of radiomics. The objective of this article is to discuss some parameters that affect the performance of texture metrics and propose recommendations that can guide both the design and evaluation of future radiomics studies. CONCLUSION: A variety of texture-extraction techniques are used to assess clinical imaging data. Currently, no consensus exists regarding workflow, including acquisition, extraction, or reporting of variable settings leading to poor reproducibility.

Reliability of CT-based texture features: Phantom study.

OBJECTIVE: To determine the intra-, inter- and test-retest variability of CT-based texture analysis (CTTA) metrics. MATERIALS AND METHODS: In this study, we conducted a series of CT imaging experiments using a texture phantom to evaluate the performance of a CTTA panel on routine abdominal imaging protocols. The phantom comprises of three different regions with various textures found in tumors. The phantom was scanned on two CT scanners viz. the Philips Brilliance 64 CT and Toshiba Aquilion Prime 160 CT scanners. The intra-scanner variability of the CTTA metrics was evaluated across imaging parameters such as slice thickness, field of view, post-reconstruction filtering, tube voltage, and tube current. For each scanner and scanning parameter combination, we evaluated the performance of eight different types of texture quantification techniques on a predetermined region of interest (ROI) within the phantom image using 235 different texture metrics. We conducted the repeatability (test-retest) and robustness (intra-scanner) test on both the scanners and the reproducibility test was conducted by comparing the inter-scanner differences in the repeatability and robustness to identify reliable CTTA metrics. Reliable metrics are those metrics that are repeatable, reproducible and robust. RESULTS: As expected, the robustness, repeatability and reproducibility of CTTA metrics are variably sensitive to various scanner and scanning parameters. Entropy of Fast Fourier Transform-based texture metrics was overall most reliable across the two scanners and scanning conditions. Post-processing techniques that reduce image noise while preserving the underlying edges associated with true anatomy or pathology bring about significant differences in radiomic reliability compared to when they were not used. CONCLUSION: Following large-scale validation, identification of reliable CTTA metrics can aid in conducting large-scale multicenter CTTA analysis using sample sets acquired using different imaging protocols, scanners etc.

Differentiation of Predominantly Solid Enhancing Lipid-Poor Renal Cell Masses by Use of Contrast-Enhanced CT: Evaluating the Role of Texture in Tumor Subtyping.

OBJECTIVE: The purpose of this study was to assess the accuracy of a panel of texture features extracted from clinical CT in differentiating benign from malignant solid enhancing lipid-poor renal masses. MATERIALS AND METHODS: In a retrospective case-control study of 174 patients with predominantly solid nonmacroscopic fat-containing enhancing renal masses, 129 cases of malignant renal cell carcinoma were found, including clear cell, papillary, and chromophobe subtypes. Benign renal masses-oncocytoma and lipid-poor angiomyolipoma-were found in 45 patients. Whole-lesion ROIs were manually segmented and coregistered from the standard-of-care multiphase contrast-enhanced CT (CECT) scans of these patients. Pathologic diagnosis of all tumors was obtained after surgical resection. CECT images of the renal masses were used as inputs to a CECT texture analysis panel comprising 31 texture metrics derived with six texture methods. Stepwise logistic regression analysis was used to select the best predictor among all candidate predictors from each of the texture methods, and their performance was quantified by AUC. RESULTS: Among the texture predictors aiding renal mass subtyping were entropy, entropy of fast-Fourier transform magnitude, mean, uniformity, information measure of correlation 2, and sum of averages. These metrics had AUC values ranging from good (0.80) to excellent (0.98) across the various subtype comparisons. The overall CECT-based tumor texture model had an AUC of 0.87 (p < 0.05) for differentiating benign from malignant renal masses. CONCLUSION: The CT texture statistical model studied was accurate for differentiating benign from malignant solid enhancing lipid-poor renal masses.

Accuracy of Contrast-Enhanced Ultrasound Compared With Magnetic Resonance Imaging in Assessing the Tumor Response After Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVES: This pilot study compared contrast enhanced ultrasound (US) with contrast-enhanced magnetic resonance imaging (MRI) in assessing the treatment response in patients with breast cancer receiving preoperative neoadjuvant chemotherapy (NAC). METHODS: This prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study included 30 patients, from January 2014 to October 2015, with invasive breast cancer detected by mammography, conventional US imaging, or both and scheduled for NAC. Informed consent was obtained. Contrast-enhanced US (perflutren lipid microspheres, 10 µL/kg) and MRI (gadopentetate dimeglumine, 0.1 mmol/kg) scans were performed at baseline before starting NAC and after completing NAC before surgery. Results of the imaging techniques were compared with each other and with histopathologic findings obtained at surgery using the Spearman correlation. Tumor size and enhancement parameters were compared for 15 patients with contrast-enhanced US, MRI, and surgical pathologic findings. RESULTS: The median tumor size at baseline was 3.1 cm on both contrast-enhanced US and MRI scans. The Spearman correlation showed strong agreement in tumor size at baseline between contrast-enhanced US and MRI (r = 0.88; P < .001) but less agreement in tumor size after NAC (r = 0.66; P = .004). Trends suggested that contrast-enhanced US (r = 0.75; P < .001) had a better correlation than MRI (r = 0.42; P = .095) with tumor size at surgery. Contrast-enhanced US was as effective as MRI in predicting a complete pathologic response (4 patients; 75.0% accuracy for both) and a non-complete pathologic response (11 patients; 72.7% accuracy for both). CONCLUSIONS: Contrast enhanced US is a valuable imaging modality for assessing the treatment response in patients receiving NAC and had a comparable correlation as MRI with breast cancer size at surgery.

Personalized 3D printed model of kidney and tumor anatomy: a useful tool for patient education.

PURPOSE: To assess the impact of 3D printed models of renal tumor on patient's understanding of their conditions. Patient understanding of their medical condition and treatment satisfaction has gained increasing attention in medicine. Novel technologies such as additive manufacturing [also termed three-dimensional (3D) printing] may play a role in patient education. METHODS: A prospective pilot study was conducted, and seven patients with a primary diagnosis of kidney tumor who were being considered for partial nephrectomy were included after informed consent. All patients underwent four-phase multi-detector computerized tomography (MDCT) scanning from which renal volume data were extracted to create life-size patient-specific 3D printed models. Patient knowledge and understanding were evaluated before and after 3D model presentation. Patients' satisfaction with their specific 3D printed model was also assessed through a visual scale. RESULTS: After viewing their personal 3D kidney model, patients demonstrated an improvement in understanding of basic kidney physiology by 16.7 % (p = 0.018), kidney anatomy by 50 % (p = 0.026), tumor characteristics by 39.3 % (p = 0.068) and the planned surgical procedure by 44.6 % (p = 0.026). CONCLUSION: Presented herein is the initial clinical experience with 3D printing to facilitate patient's pre-surgical understanding of their kidney tumor and surgery.

Cortical activation associated with muscle synergies of the human male pelvic floor.

Human pelvic floor muscles have been shown to operate synergistically with a wide variety of muscles, which has been suggested to be an important contributor to continence and pelvic stability during functional tasks. However, the neural mechanism of pelvic floor muscle synergies remains unknown. Here, we test the hypothesis that activation in motor cortical regions associated with pelvic floor activation are part of the neural substrate for such synergies. We first use electromyographic recordings to extend previous findings and demonstrate that pelvic floor muscles activate synergistically during voluntary activation of gluteal muscles, but not during voluntary activation of finger muscles. We then show, using functional magnetic resonance imaging (fMRI), that a region of the medial wall of the precentral gyrus consistently activates during both voluntary pelvic floor muscle activation and voluntary gluteal activation, but not during voluntary finger activation. We finally confirm, using transcranial magnetic stimulation, that the fMRI-identified medial wall region is likely to generate pelvic floor muscle activation. Thus, muscle synergies of the human male pelvic floor appear to involve activation of motor cortical areas associated with pelvic floor control.

Quantitative assessment of solid renal masses by contrast-enhanced ultrasound with time-intensity curves: how we do it.

PURPOSE: To discuss the evaluation of the enhancement curve over time of the major renal cell carcinoma (RCC) subtypes, oncocytoma, and lipid-poor angiomyolipoma, to aid in the preoperative differentiation of these entities. Differentiation of these lesions is important, given the different prognoses of the subtypes, as well as the desire to avoid resecting benign lesions. METHODS: We discuss findings from CT, MR, and US, but with a special emphasis on contrast-enhanced ultrasound (CEUS). CEUS technique is described, as well as time-intensity curve analysis. RESULTS: Examples of each of the major RCC subtypes (clear cell, papillary, and chromophobe) are shown, as well as examples of oncocytoma and lipid-poor angiomyolipoma. For each lesion, the time-intensity curve of enhancement on CEUS is reviewed, and correlated with the enhancement curve over time reported for multiphase CT and MR. CONCLUSIONS: Preoperative differentiation of the most common solid renal masses is important, and the time-intensity curves of these lesions show some distinguishing features that can aid in this differentiation. The use of CEUS is increasing, and as a modality it is especially well suited to the evaluation of the time-intensity curve.

CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method.

PURPOSE: There are distinct quantifiable features characterizing renal cell carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement, tumor heterogeneity, and percent contrast washout. While qualitative visual impressions often suffice for diagnosis, quantitative metrics if developed and validated can add to the information available from standard of care diagnostic imaging. The purpose of this study is to assess the use of quantitative enhancement metrics in predicting the Fuhrman grade of clear cell RCC. MATERIALS AND METHODS: 65 multiphase CT examinations with clear cell RCCs were utilized, 44 tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor segmentation, the following data were extracted: histogram analysis of voxel-based whole lesion attenuation in each phase, enhancement and washout using mean, median, skewness, kurtosis, standard deviation, and interquartile range. RESULTS: Statistically significant difference was observed in 4 measured parameters between grades 1-2 and grades 3-4: interquartile range of nephrographic attenuation values, standard deviation of absolute enhancement, as well as interquartile range and standard deviation of residual nephrographic enhancement. Interquartile range of nephrographic attenuation values was 292.86 HU for grades 1-2 and 241.19 HU for grades 3-4 (p value 0.02). Standard deviation of absolute enhancement was 41.26 HU for grades 1-2 and 34.66 HU for grades 3-4 (p value 0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement for grades 1-2 and 235.57 HU for grades 3-4 (p value 0.02), and standard deviation of the same was 42.45 HU for grades 1-2 and 37.11 for grades 3-4 (p value 0.04). CONCLUSION: Our results indicate that absolute enhancement is more heterogeneous for lower grade tumors and that attenuation and residual enhancement in nephrographic phase is more heterogeneous for lower grade tumors. This represents an important step in devising a predictive non-invasive model to predict the nucleolar grade.

Contrast-Enhanced Sonography for Monitoring Neoadjuvant Chemotherapy in Soft Tissue Sarcomas.

Neoadjuvant chemotherapy is a mainstay in treating soft tissue sarcomas. Soft tissue sarcomas can show an increase in size and central necrosis, with a decrease in the viable tumor, as an initial response to neoadjuvant chemotherapy. Thus, the maximum tumor diameter may not reliably assess the response to this therapy. Contrast-enhanced sonography may address this limitation. We evaluated 4 patients with soft tissue sarcomas by contrast-enhanced sonography, performed concomitantly with conventional imaging (computed tomography, magnetic resonance imaging, or positron emission tomography). Quantitative analysis was also performed on 1 sarcoma. A viable, enhancing tumor versus tumor necrosis was nearly identical on contrast-enhanced sonography and conventional imaging. Preliminary results demonstrate potential for contrast-enhanced sonographic monitoring of soft tissue sarcomas during neoadjuvant chemotherapy.

Image coregistration: quantitative processing framework for the assessment of brain lesions.

The quantitative, multiparametric assessment of brain lesions requires coregistering different parameters derived from MRI sequences. This will be followed by analysis of the voxel values of the ROI within the sequences and calculated parametric maps, and deriving multiparametric models to classify imaging data. There is a need for an intuitive, automated quantitative processing framework that is generalized and adaptable to different clinical and research questions. As such flexible frameworks have not been previously described, we proceeded to construct a quantitative post-processing framework with commonly available software components. Matlab was chosen as the programming/integration environment, and SPM was chosen as the coregistration component. Matlab routines were created to extract and concatenate the coregistration transforms, take the coregistered MRI sequences as inputs to the process, allow specification of the ROI, and store the voxel values to the database for statistical analysis. The functionality of the framework was validated using brain tumor MRI cases. The implementation of this quantitative post-processing framework enables intuitive creation of multiple parameters for each voxel, facilitating near real-time in-depth voxel-wise analysis. Our initial empirical evaluation of the framework is an increased usage of analysis requiring post-processing and increased number of simultaneous research activities by clinicians and researchers with non-technical backgrounds. We show that common software components can be utilized to implement an intuitive real-time quantitative post-processing framework, resulting in improved scalability and increased adoption of post-processing needed to answer important diagnostic questions.

Conditional generative learning for medical image imputation.

Image imputation refers to the task of generating a type of medical image given images of another type. This task becomes challenging when the difference between the available images, and the image to be imputed is large. In this manuscript, one such application is considered. It is derived from the dynamic contrast enhanced computed tomography (CECT) imaging of the kidneys: given an incomplete sequence of three CECT images, we are required to impute the missing image. This task is posed as one of probabilistic inference and a generative algorithm to generate samples of the imputed image, conditioned on the available images, is developed, trained, and tested. The output of this algorithm is the "best guess" of the imputed image, and a pixel-wise image of variance in the imputation. It is demonstrated that this best guess is more accurate than those generated by other, deterministic deep-learning based algorithms, including ones which utilize additional information and more complex loss terms. It is also shown that the pixel-wise variance image, which quantifies the confidence in the reconstruction, can be used to determine whether the result of the imputation meets a specified accuracy threshold and is therefore appropriate for a downstream task.